Incidence and determinants of fracture risk in 8,348 Mongolian schoolchildren: secondary analysis of data from a randomised controlled trial

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Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Incidence and determinants of fracture risk in 8,348 Mongolian schoolchildren: secondary analysis of data from a randomised controlled trial Barnaby Casson , David A Jolliffe , Sukhbaatar Ariunbuyan , Baigal Delgerekh , Tumenjargal Turmunkh , Uyanga Buyanjargal , View ORCID Profile Adrian R Martineau , Davaasambuu Ganmaa doi: https://doi.org/10.1101/2025.10.31.25339221 Barnaby Casson 1 School of Medicine, Newcastle University , Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site David A Jolliffe 2 Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London , 4 Newark St, London E1 2AT, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sukhbaatar Ariunbuyan 3 Division of Oral and Maxillofacial Oncology and Surgical Sciences, Graduate School of Dentistry, Tohoku University , 4⍰1 Seiryo, Aoba, Sendai, Miyagi 980⍰8575, Japan 4 Laboratory of Biomedical Engineering for Cancer, Graduate School of Biomedical Engineering, Tohoku University , 4⍰1 Seiryo, Aoba, Sendai, Miyagi 980⍰8575, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site Baigal Delgerekh 5 Mongolian Health Initiative , Ulaanbaatar, Mongolia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Tumenjargal Turmunkh 5 Mongolian Health Initiative , Ulaanbaatar, Mongolia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Uyanga Buyanjargal 5 Mongolian Health Initiative , Ulaanbaatar, Mongolia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Adrian R Martineau 2 Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London , 4 Newark St, London E1 2AT, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Adrian R Martineau For correspondence: gdavaasa{at}hsph.harvard.edu a.martineau{at}qmul.ac.uk Davaasambuu Ganmaa 6 The Department of Nutrition , Harvard T.H. Chan School of Public Health, Building 2, Room 211, 655 Huntington Ave, Boston, Massachusetts 02115, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: gdavaasa{at}hsph.harvard.edu a.martineau{at}qmul.ac.uk Abstract Full Text Info/History Metrics Data/Code Preview PDF ABSTRACT Background Data on incidence and determinants of fracture risk among children living in non-Western settings are limited. The predictive value of radial quantitative ultrasound (QUS) for fracture risk in children remains uncertain. Methods We conducted secondary analyses of data from 8,348 schoolchildren aged 6-13 years living in Ulaanbaatar, Mongolia, who participated in a population-based randomised controlled trial of vitamin D supplementation with 3-year follow-up. Radial speed-of-sound (SOS) was measured at baseline in a subset of 1,456 children. Multivariable Poisson regression was used to estimate fracture incidence, identify determinants of fracture risk, and test whether radial SOS measurements predicted fracture risk. Results A total of 614 fractures occurred in 521 children over 24,719.3 person-years of follow-up. Overall fracture incidence was 24.9 per 1,000 person-years (95% CI 22.9 to 26.9). Fracture risk was higher in boys vs. girls (adjusted incidence rate ratio [aIRR] 2.10, 95% CI 1.77 to 2.49, P<0.0001) and in older vs. younger children (aIRR 1.18 per additional year of age, 95% CI 1.13 to 1.24, P<0.0001), peaking at age 14 in both boys (87.4 fractures per 1,000 boys per year, 95% CI 63.3 to 117.8) and girls (24.9 fractures per 1,000 girls per year, 95% CI 12.4 to 44.5, respectively). Fracture risk was also higher in children who smoked tobacco vs. those who did not (aIRR 2.20, 95% CI 1.09 to 4.43, P=0.03), while children whose parents were homeowners vs. non-homeowners had lower fracture risk (aIRR 0.83, 95% CI 0.69 to 0.99, P=0.048). Baseline radial SOS did not associate with fracture risk (IRR 0.99; 95% CI 0.99 to 1.00, P=0.31). Conclusions Fracture incidence among schoolchildren in Mongolia is higher than in Western settings, particularly for boys. Male sex, older age and tobacco smoking were risk factors in this population, while parental home ownership (denoting higher socio-economic status) was protective. Baseline radial SOS did not predict fracture risk in this population. INTRODUCTION An estimated 31 million fractures occurred globally in 2021 among children aged less than 14 years, constituting a substantial source of morbidity, school absence and healthcare expenditure. 1 Epidemiological studies conducted in Europe and North America have identified increasing age, male sex, pubertal onset, smoking and lower socioeconomic position as risk factors for fractures. 2 - 9 Quantitative ultrasound (QUS) has been proposed as a potential low-cost, non-invasive correlate of fracture risk. Cross-sectional studies have reported that radial and tibial speed of sound (SOS) measurements associate with age, pubertal stage and socioeconomic position in adolescents, 10 - 12 while case-control studies have reported lower SOS readings in individuals who have experienced a fracture vs. those who have not. 13 - 15 However, existing research in this area has largely been conducted in European and North American settings, and data on the predictive value of QUS for incident fracture from low- or middle-income settings, where fracture incidence rates are relatively high, 16 are lacking. An opportunity to address this evidence gap arose following completion of a 3-year population-based randomised controlled trial of vitamin D supplementation, which enrolled 8,851 schoolchildren living in Ulaanbaatar, Mongolia, and captured fracture incidence as a secondary outcome. 17 Details of potential risk factors for fracture were collected at baseline. A subset of 1,456 participants additionally underwent radial SOS measurement at baseline, of whom 1,357 had a repeat measurement at 3-year follow-up. Here, we report results from secondary analyses of trial data, conducted to identify risk factors for incident fractures in this population; to determine whether baseline radial SOS measurements were predictive of subsequent fracture risk; and to evaluate determinants of baseline radial SOS and change in radial SOS over 3-year follow-up. METHODS Study Design, Setting and Participants We conducted a parallel two-arm double-blind individually randomised placebo-controlled trial in 18 public schools across Ulaanbaatar, Mongolia, as previously described. 17 The primary outcome of the trial was acquisition of latent tuberculosis infection, as indicated by conversion of QuantiFERON-TB Gold In-tube (QFT) assay from negative to positive; fracture incidence was a secondary outcome. The current manuscript reports findings from a secondary analysis relating to determinants of fracture risk in the main study population of 8,348 participants, of whom 1,456 underwent radial SOS measurements at baseline. Inclusion criteria for the trial were children aged 6–13 years at time of screening, attending a participating school and the provision of written informed assent from the child and written informed consent from a parent or guardian. Exclusion criteria were a positive QFT assay result, the presence of conditions associated with vitamin D hypersensitivity (e.g. primary hyperparathyroidism or sarcoidosis), having immunocompromised status (e.g. taking immunosuppressive or cytotoxic therapy), the use of vitamin D supplements, clinical signs of rickets, or plans to move out of Ulaanbaatar during the study period. The trial was approved by institutional review boards of the Mongolian Ministry of Health, Mongolian National University, and Harvard T. H. Chan School of Public Health, Boston, USA (ref 14-0513). The trial is registered with clinicaltrials.gov , ref NCT02276755 . Data collection Baseline demographic, lifestyle and nutritional data were collected for all 8,348 participants via parent-reported questionnaire, as described elsewhere. 17 These included: age, sex, ethnicity, outdoor activity, environmental tobacco smoke exposure, active smoking status, family income, level of parental education, home ownership, and type of home and dietary calcium intake. At baseline, 2- and 3-year follow-up, children additionally underwent measurements for height using a portable stadiometer (SECA, Hamburg, Germany), weight using and a digital floor scale (SECA), bioelectric impedance using a body composition analyser (SC-331S, Tanita, Tokyo, Japan), and blood donation for determination of circulating serum 25(OH)D concentrations by VIDAS 25OH vitamin D total enzyme-linked fluorescent assay (bioMérieux, Marcy-l’Étoile, France). At 2- and 3-year follow-up, fracture incidence outcome data were collected by self-reported questionnaires, as previously reported. 18 Z-scores for height-for-age and BMI-for-age were computed using the 2007 WHO growth reference standards. Non-zero serum 25(OH)D concentrations were standardised using a published method, 19 utilising a set of 40 reference samples provided by the Vitamin D External Quality Assessment Scheme (DEQAS, http://www.deqas.org/ ). Values were then adjusted using a sinusoidal model to account for seasonal variation, as previously described. 20 In 14 participating schools, a subset of 1,465 children was randomly selected to be included in the QUS sub-study and additionally underwent measurement for radial SOS at the distal one-third of the radius using a Sunlight MiniOmni portable bone sonometer (BeamMed, Petah Tikva, Israel), with measurements taken on the non-dominant arm unless the child was injured. Of these, 1,357 had a repeat radial SOS measurement at 3-year follow-up. For each of these participants, change in radial SOS from baseline to follow-up (Δ-SOS) was calculated by subtracting the baseline reading from the follow-up reading. Statistical analysis Data were analysed in Python 3.12.4 with statsmodels 0.14.2 and pandas 2.2.2. Fracture risk was estimated using Poisson models, to allow for repeat fractures and variable follow-up duration, producing incidence rate ratios (IRRs) along with 95% confidence intervals and associated p values. Determinants of baseline radial SOS and Δ-SOS were evaluated using ordinary least squares to fit linear models, producing mean differences along with 95% confidence intervals and associated p values. For all outcomes, univariate factors which were significant at the 10% alpha threshold were carried through to a multivariable model. A multiplication factor of 1000 was applied to radial SOS. Missing outcome data was infrequent: 8,348/8,851 (94.3%) randomised participants contributed fracture outcome data, while 1,357/1,465 (92.6%) of participants who had baseline radial SOS measurements also had follow-up measurements. RESULTS Participants Table 1 presents baseline characteristics of the 8,348 trial participants who contributed data to the analysis of determinants of fracture risk, and of the subset of 1,465 participants who also underwent radial SOS measurement. Mean age was 9.4 years (SD 1.6), 49.4% were female and 92.3% were of Khalkh ethnic origin. These and other baseline characteristics in the overall study population were well matched with the subset of participants who contributed SOS data. Total follow-up time was 24,719.3 person-years; average participant follow-up was 2.96 years (SD 0.27). View this table: View inline View popup Download powerpoint Table 1. Participant characteristics at baseline Determinants of fracture risk A total of 614 fractures occurred in 521 children, of whom 434 experienced one fracture, 81 experienced two fractures and 6 experienced three fractures. Upper limb fractures were most common (436 arising in 374 children), followed by lower limb fractures (138 arising in 134 children) and fractures at other anatomical sites (40 arising in 40 children). Overall fracture incidence rate was 24.9 per 1000 person-years (95% CI 22.9 to 26.9). Determinants of fracture risk are presented in Table 2 . Fracture risk was higher with increasing age (adjusted incidence rate ratio [aIRR] 1.18 per additional year of age, 95% CI 1.13 to 1.24, p<0.0001); in males vs. females (aIRR 2.10, 95% CI 1.77 to 2.49, p<0.0001) and in tobacco smokers vs. non-smokers (aIRR 2.20, 95% CI 1.09 to 4.43, p=0.027). Risk of fracture was lower in children whose parents were homeowners vs. non-homeowners (aIRR 0.83, 95% CI 0.69 to 0.99, p=0.048). Figure 2 illustrates that fracture incidence rate (IR) peaked at age 14 both in males (IR 87.4 fractures per 1,000 children per year, 95% CI 63.3 to 117.8) and in females (IR 24.9 fractures per 1,000 children per year, 95% CI 12.4 to 44.5, respectively). Body fat percentage, baseline vitamin D status and level of outdoor activity associated with fracture risk on univariate analysis, but not in multivariable analysis. No other independent variable investigated associated with risk of fracture on univariate analysis, including baseline radial SOS, which was not associated with fracture risk (IRR 0.99; 95% CI 0.99 to 1.00, p=0.31). View this table: View inline View popup Download powerpoint Table 2. Determinants of fracture incidence Download figure Open in new tab Figure 1. Participant flow Footnotes: QFT: QuantiFERON-TB Gold in-tube assay; SOS: radial quantitative ultrasound (speed of sound) Download figure Open in new tab Figure 2. Fracture incidence by age and sex. Lines represent point estimates for fracture incidence rates. Shaded areas represent 95% confidence intervals. Determinants of radial SOS Table 3 presents the determinants of baseline radial SOS. The following factors were independently associated with baseline radial SOS: age (adjusted mean difference [aMD] 15.06 m/s per additional year of age, 95% CI 11.12 to 19.00, P<0.0001) and baseline serum 25(OH)D concentration (aMD 2.32 m/s per additional ng/mL, 95% CI 0.77 to 3.86, P=0.003). Determinants of change in radial SOS over 3-year follow-up (Δ-SOS) are presented in Table 4 . Δ-SOS was positively associated with height-for-age Z-score (aMD 15.41m/s per additional Z-score point, 95% CI 7.44 to 23.38, p=.0002) and was lower in males vs. females (aMD −79.82 m/s, 95% CI −94.84 to - 64.80, P<0.0001). Percentage body fat and level of parental education associated with Δ-SOS in univariate analysis but did not remain significant after fitting them into the multivariable model. View this table: View inline View popup Download powerpoint Table 3. Determinants of baseline radial speed of sound View this table: View inline View popup Download powerpoint Table 4. Determinants of delta-radial SOS DISCUSSION In this prospective cohort study of 8,348 Mongolian schoolchildren - which to our knowledge is the largest to investigate the predictive potential of radial quantitative ultrasound for fractures and the first to do so in this setting - we identified (i) a high overall fracture incidence of 24.9 events per 1,000 person-years; (ii) markedly elevated fracture risk in boys, older children and active smokers, with a protective association for parental home-ownership; (iii) no prospective association between baseline QUS measurement and risk of subsequent fractures; (iv) independent associations between higher age and baseline vitamin D status with higher baseline radial SOS; and v) divergent trajectories in radial SOS, showing gains in girls but losses in boys over 3-year follow-up. Overall fracture incidence in this population was considerably higher than has previously been reported in Europe, 21 - 23 North America, 24 Africa 25 and elsewhere in Asia. 26 Our findings with respect to age and sex as risk factors align with previously published global patterns showing increasing risk in during adolescence, particularly in males. 2 , 3 , 7 , 27 The protective effect of parental home ownership in the absence of associations for other socioeconomic factors mirrors conflicting findings regarding the influence of socioeconomic deprivation on fracture risk from other settings. 6 - 8 Our finding that tobacco smoking is a risk factor for fractures in children is consistent with findings of smaller European and North-American studies that have linked adolescent tobacco use to reduced bone mass and higher fracture risk. 7 , 8 Evidence for radial QUS readings as a predictor of fracture risk in children is inconsistent. Early case–control work at phalangeal and tibial sites showed lower SOS in injured participants, 10 , 11 whereas recent reviews conclude that paediatric data remain insufficient and heterogeneous, particularly for the radial SOS. 28 Our null findings extend the literature by providing the first large, prospective test of distal radial SOS in an Asian adolescent population, and reinforce calls to evaluate alternative QUS indices (e.g., broadband ultrasound attenuation, stiffness parameters) or multi-site composites for prediction of fracture risk. The pronounced sex divergence in Δ-SOS over 3-year follow-up (girls +51 m/s vs. boys –28 m/s) likely reflects earlier pubertal onset and oestrogen-mediated cortical consolidation in girls, versus a transient deceleration before the male pubertal growth spurt. The positive associations between baseline vitamin D status and linear growth for baseline radial SOS underscore the sensitivity of QUS to both mineralisation and size-related acoustic pathways. Our study has several strengths, including a large population size, prospective design, comprehensive characterisation for a range of demographic, anthropometric, biological and biochemical factors and the standardised laboratory calibration of serum 25(OH)D concentrations. There were also some limitations: radial SOS, while a useful proxy for bone stiffness, may not provide a complete picture of bone quality. Bone stiffness indices that also incorporate broadband ultrasound attenuation may reflect bone quality more accurately. Additionally, fractures were self-reported and not radiologically confirmed, introducing possible misclassification. In conclusion, we report that schoolchildren in Mongolia are at heightened risk of fracture compared with those previously studied in European, North American and other settings, with adolescent boys being at highest risk. Radial quantitative ultrasound readings did not predict fracture risk in this population. Data Availability Anonymized data may be requested from the corresponding authors to be shared subject to terms of IRB approval. DECLARATION OF INTERESTS ARM declares receipt of funding in the last 60 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd and Hyphens Pharma Ltd. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd; support for attending meetings from Pharma Nord Ltd and Abiogen Pharma Ltd; receipt of consultancy fees from DSM Nutritional Products Ltd and Qiagen Ltd; receipt of a speaker fee from the Linus Pauling Institute; participation on Data and Safety Monitoring Boards for the VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology, Pan African Clinical Trials Registry ref PACTR20200989766029) and the Trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India ( ClinicalTrials.gov ref NCT04641195 ); and unpaid work as a Programme Committee member for the Vitamin D Workshop. All other authors declare that they have no competing interests. DATA SHARING Anonymized data may be requested from the corresponding authors to be shared subject to terms of IRB approval. ACKNOWLEDGEMENTS This study was supported by an award from the United States National Institutes of Health, ref. 1R01HL122624-01. We thank all the children who participated in the trial, and their parents and guardians. We also thank independent members of the Data Safety Monitoring Board (Prof S.M. Fortune and Dr P.L. Williams, Harvard T.H. Chan School of Public Health; Profs M.F. Holick and C.R. Horsburgh, Boston University; Prof P. Enkhbaatar, University of Texas; and Dr. E. Chadraa, Minnesota State University); independent members of the Trial Steering Committee (Profs W.C. Willett, Edward L. Giovannucci and B.R. Bloom, Harvard T.H. Chan School of Public Health; Dr N. Naranbat, Gyals Medical Laboratory, Ulaanbaatar; and late Dr D. Malchinkhuu, National Center for Maternal and Child Health of Mongolia); board members at the Mongolian Health Initiative (Dr J. Tuyatsetseg, Mongolian University of Science and Technology; Dr J. Amarsanaa, Happy Veritas Laboratory, Ulaanbaatar; Drs P. Erkhembulgan and G. Batbaatar, Mongolian National University of Medical Sciences; Prof M.C. Elliott, Harvard University; and Mr. Ts. Munh-Orgil, Member of the Mongolian Parliament); and the following individuals for advice and helpful discussions: Dr Winthrop Burr (Anadyne Psychotherapy Inc) and Dr. Masae Kawamura at Qiagen USA. References 1. ↵ Global Burden of Disease Collaborative Network . Global Burden of Disease Study 2021 (GBD 2021) . Seattle, United States: Institute for Health Metrics and Evaluation (IHME) Published online 2024 . 2. ↵ Clark EM . The epidemiology of fractures in otherwise healthy children . Curr Osteoporos Rep 2014 ; 12 ( 3 ): 272 – 8 . OpenUrl PubMed 3. ↵ Rennie L , Court-Brown CM , Mok JY , Beattie TF . The epidemiology of fractures in children . Injury 2007 ; 38 ( 8 ): 913 – 22 . OpenUrl CrossRef PubMed Web of Science 4. Lyons RA , Delahunty AM , Kraus D , et al. Children’s fractures: a population based study . Inj Prev 1999 ; 5 ( 2 ): 129 – 32 . 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Share Incidence and determinants of fracture risk in 8,348 Mongolian schoolchildren: secondary analysis of data from a randomised controlled trial Barnaby Casson , David A Jolliffe , Sukhbaatar Ariunbuyan , Baigal Delgerekh , Tumenjargal Turmunkh , Uyanga Buyanjargal , Adrian R Martineau , Davaasambuu Ganmaa medRxiv 2025.10.31.25339221; doi: https://doi.org/10.1101/2025.10.31.25339221 Share This Article: Copy Citation Tools Incidence and determinants of fracture risk in 8,348 Mongolian schoolchildren: secondary analysis of data from a randomised controlled trial Barnaby Casson , David A Jolliffe , Sukhbaatar Ariunbuyan , Baigal Delgerekh , Tumenjargal Turmunkh , Uyanga Buyanjargal , Adrian R Martineau , Davaasambuu Ganmaa medRxiv 2025.10.31.25339221; doi: https://doi.org/10.1101/2025.10.31.25339221 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Orthopedics Subject Areas All Articles Addiction Medicine (568) Allergy and Immunology (863) Anesthesia (300) Cardiovascular Medicine (4441) Dentistry and Oral Medicine (444) Dermatology (383) Emergency Medicine (608) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1510) Epidemiology (15229) Forensic Medicine (30) Gastroenterology (1126) Genetic and Genomic Medicine (6606) Geriatric Medicine (668) Health Economics (998) Health Informatics (4541) Health Policy (1369) Health Systems and Quality Improvement (1613) Hematology (543) HIV/AIDS (1265) Infectious Diseases (except HIV/AIDS) (15923) Intensive Care and Critical Care Medicine (1103) Medical Education (623) Medical Ethics (147) Nephrology (668) Neurology (6604) Nursing (346) Nutrition (998) Obstetrics and Gynecology (1145) Occupational and Environmental Health (957) Oncology (3334) Ophthalmology (974) Orthopedics (369) Otolaryngology (420) Pain Medicine (436) Palliative Medicine (130) Pathology (663) Pediatrics (1693) Pharmacology and Therapeutics (692) Primary Care Research (711) Psychiatry and Clinical Psychology (5448) Public and Global Health (9235) Radiology and Imaging (2200) Rehabilitation Medicine and Physical Therapy (1370) Respiratory Medicine (1196) Rheumatology (594) Sexual and Reproductive Health (713) Sports Medicine (530) Surgery (712) Toxicology (99) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a017cb551bb9aa64',t:'MTc3OTc0NjIzMA=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();